Direct electrophilic and radical isoperfluoropropylation with i-C3F7-Iodine(III) reagent (PFPI reagent)

The isoperfluoropropyl group (i-C3F7) is an emerging motif in pharmaceuticals, agrichemicals and functional materials. However, isoperfluoropropylated compounds remain largely underexplored, presumably due to the lack of efficient access to these compounds. Herein, we disclose the practical and efficient isoperfluoropropylation of aromatic C-H bonds through the invention of a hypervalent-iodine-based reagent-PFPI reagent, that proceeds via a Ag-X coupling process. The activation of the PFPI reagent without any catalysts or additives was demonstrated in the synthesis of isoperfluoropropylated electron-rich heterocycles, while its activity under photoredox catalysis was shown in the synthesis of isoperfluoropropylated non-activated arenes. Detailed mechanistic experiments and DFT calculations revealed a SET-induced concerted mechanistic pathway in the photoredox reactions. In addition, the unique conformation of i-C3F7 in products, that involved intramolecular hydrogen bond was investigated by X-ray single-crystal diffraction and variable-temperature NMR experiments.


Amide-type chloroiodine(III) intermediate
N-acetyl-1-chloro-1,2-benziodamine-3-(1H)-one was obtained as a colorless solid (4.55 g, 94% yield). In a nitrogen-filled glove box, an oven-dried crimp cap vessel with Teflon-coated stirrer bar was charged with silver fluoride (0.64 g, 5.0 mmol, 1.0 equiv.) and was brought under an atmosphere of dry nitrogen. To this vessel, anhydrous acetonitrile (20 mL) and hexafluoropropylene (1atm, balloon and adequate) were added, and the mixture was stirred at ice-water bath in the dark until silver fluoride precipitate dissolved completely. Then this solution was added to another oven-dried vessel, which filling with 1-chloro-1,2-benziodoxol-3-(1H)-one (1.44 g, 5.1 mmol, 1.02 equiv.) and 4 Å molecular sieves (100 mg). The reaction mixture was stirred at ambient temperature in the dark for 1 hours. The reaction mixture was filtered over a sintered-glass funnel with a tightly packed pad of Celite (0.5 cm thick) under dry nitrogen atmosphere, and the filter cake was rinsed with additional anhydrous acetonitrile (5 -10 mL). The solvent was evaporated under reduced pressure and crude solid product washed with anhydrous Et2O (10 -20 mL). Then, the product was obtained by anhydrous DCM leaching in ultrasonic generator under dry nitrogen atmosphere and vacuum evaporated of solvent. The solid was dried for 1 h under high vacuum to give 1-isoperfluoropropyl-1,2-benziodoxol-3-(1H)-one as off white solid (1.48 g, 71% yield).
Under the Schlenk line, an oven-dried Schlenk flask with Teflon-coated stirrer bar was charged with silver fluoride (0.64 g, 5.0 mmol, 1.0 equiv.) and was brought under an atmosphere of dry nitrogen.
To this vessel, anhydrous acetonitrile (20 mL) and hexafluoropropylene (1atm, balloon and adequate) were added, and the mixture was stirred at ice-water bath in the dark until silver fluoride precipitate dissolved completely. Then this solution was added to another oven-dried vessel, which filling with 1-chloro-1,2-benziodoxol-3-(1H)-one (1.44 g, 5.1 mmol, 1.02 equiv.) and 4 Å molecular sieves (100 mg). The reaction mixture was stirred at ambient temperature in the dark for 1 hours.
Under nitrogen protection, the filtrate was extracted through catheter tied with filter paper and transferred to another drying bottle, and the filter cake was rinsed with additional anhydrous acetonitrile (5 -10 mL). The solvent was evaporated under reduced pressure and crude solid product washed with anhydrous Et2O (10 -20 mL). Then, the product was obtained by anhydrous DCM leaching in ultrasonic generator under dry nitrogen atmosphere and vacuum evaporated of solvent. The solid was dried for 1 h under high vacuum to give 1-isoperfluoropropyl-1,2benziodoxol-3-(1H)-one as off white solid (1.23 g, 59% yield).
In a nitrogen-filled glove box, an oven-dried crimp cap vessel with Teflon-coated stirrer bar was charged with silver fluoride (0.64 g, 5.0 mmol, 1.0 equiv.) and was brought under an atmosphere of dry nitrogen. To this vessel, anhydrous acetonitrile (20 mL) and hexafluoropropylene (1atm, balloon and adequate) were added, and the mixture was stirred at ice-water bath in the dark until silver fluoride precipitate dissolved completely. Then this solution was added to another oven-dried vessel, which filling with 1-acetoxy-1,2-benziodoxol-3-(1H)-one (1.56 g, 5.1 mmol, 1.02 equiv.) and 4 Å molecular sieves (100 mg). The reaction mixture was stirred at ambient temperature in the dark for 1 hours. The reaction mixture was filtered over a sintered-glass funnel with a tightly packed pad of Celite (0.5 cm thick) under dry nitrogen atmosphere, and the filter cake was rinsed with additional anhydrous acetonitrile (5 -10 mL). The solvent was evaporated under reduced pressure and crude solid product washed with anhydrous Et2O (10 -20 mL). Then, the product was obtained by anhydrous DCM leaching in ultrasonic generator under dry nitrogen atmosphere and vacuum evaporated of solvent. The solid was dried for 1 h under high vacuum to give 1-isoperfluoropropyl-1,2-benziodoxol-3-(1H)-one as off white solid (1.35 g, 65% yield). Elemental analysis: C%, theoretical value: 28.87%, measured value: 28.99%. H%, theoretical value: 0.97%, measured value: 1.06%. O%, theoretical value: 7.69%, measured value: 7.54%.
In a nitrogen-filled glove box, an oven-dried crimp cap vessel with Teflon-coated stirrer bar was charged with silver fluoride (0.64 g, 5.0 mmol, 1.0 equiv.) and was brought under an atmosphere of dry nitrogen. To this vessel, anhydrous acetonitrile (20 mL) and hexafluoropropylene (1atm, balloon and adequate) were added, and the mixture was stirred at ice-water bath in the dark until S10 silver fluoride precipitate dissolved completely. Then this solution was added to another oven-dried vessel, which filling with N-acetyl-1-chloro-1,2-benziodamine-3-(1H)-one (1.65 g, 5.1 mmol, 1.02 equiv.) and 4 Å molecular sieves (100 mg). The reaction mixture was stirred at ambient temperature in the dark for 1 hours. The reaction mixture was filtered over a sintered-glass funnel with a tightly packed pad of Celite (0.5 cm thick) under dry nitrogen atmosphere, and the filter cake was rinsed with additional anhydrous acetonitrile (5 -10 mL). The solvent was evaporated under reduced pressure and crude solid product washed with anhydrous Et2O (10 -20 mL). Then, the product was obtained by anhydrous DCM leaching in ultrasonic generator under dry nitrogen atmosphere and vacuum evaporated of solvent. The solid was dried for 1 h under high vacuum to give N-acetyl-1fluoro-1,2-benziodamine-3-(1H)-one as off solid (1.28 g, 82% yield).